It is estimated that almost a third of HIV-positive patients are co-infected with hepatitis C virus. Studies examining cognitive function in co-infected groups have found worse performance on neuropsychological examinations in a number of cognitive domains compared to groups with HIV or HCV alone (Cherner et al., 2008; Clifford et al., 2005; Hilsabeck,et al., 2005; Letendre et al., 2002; Martin et al., 2004; Parsons et al., 2006; Ryan et al., 2004; von Giesen et al., 2004). Additionally, it has been reported that co-infected persons are significantly more likely to develop AIDS dementia complex (Ryan et al., 2004). Despite the consistent findings of decreased cognitive functioning in co-infection, to date, there are no published reports using neuroimaging designed to study the impact of co-infection in the CNS. There are a few published studies using MRI techniques to determine the impact of HCV mono-infection on the brain; studies implementing Magnetic Resonance Spectroscopy (MRS) in HCV have found markers associated with the breakdown of white matter integrity (Weissenborn et. al list others) similar to MRS findings in HIV. There are a limited number of studies using diffusion tensor imaging (DTI) in HIV, with findings indicating white matter compromise, even in white matter that appears normal (Stebbins et al., 2007). The neuropsychological deficits found in co-infection and the similar findings in HCV using MRS, though limited, prompt additional research specifically designed to examine the effects co-infection on the brain. Novel imaging techniques that are sensitive to white matter changes need to be employed to determine the extent of injury that occurs in co-infection, and perhaps lead to earlier diagnosis and improved treatment of neurological symptoms. We believe DTI is the best tool to examine co-infection in the CNS, due to its specific sensitivity to detect changes in white matter structural integrity. Further, as not all studies have identified a significant effect of HCV co-infection status on brain function, a multidisciplinary approach is needed inclusive of neuropsychological assessment, neuroimaging indices and laboratory data. This study will compare a sample of HIV-positive individuals to HIV/HCV co-infected individuals on DTI measures, as well as neuropsychological tests, to determine the signatures of co-infection in the brain. The proposed study will be the first to integrate these areas specifically in a co-infected population.